Two transgenic mouse lines have been investigated. In each of these lines, the protease of the human immunodeficiency virus (HIV-1) coding sequence is linked to the alphaA- crystallin promoter. In line 61, the mouse gets a cataract in utero, while the mice in the 72 line develop opacification of the lens at day 23.Each line is now homozygous for the construct. The proteins in the lenses of the two lines have been studied, and there are proteolytic changes observed in crystallins. HIV-1 protease has been shown to cleave actin and vimentin from the mouse lens. This protease also will attack alpha, beta-, and gamma-crystallins. The pattern of proteolytic fragmentation in the lenses of these animals, however, does not match the pattern that is obtained when purified crystallins are incubated with recombinant HIV-1 protease. That the cataract is caused by the HIV-1 protease is irrefutable because specific inhibitors of this protease prevent cataract formation. The data suggest that the HIV- 1 protease starts the process of cataract formation, but other protease in the lens may cause much of the proteolysis subsequently. These animals may give us an opportunity to test the hypothesis that although many initiating events may start the cataract process, opacification of the lens evolves from a limited number of pathways.